Investigation of the insulin sensitive CNS glucoregulator will continue to elucidate its role in the regulation of blood glucose levels in conscious, non anesthetized dogs. In animals previously equipped with permanent, indwelling cannulae in the internal carotid artery and in the portal vein, the effect of intracarotid insulin injection will be compared to the effect seen following intraportal injection of identical doses of insulin (on different dogs) in the same dogs. Peripheral venous blood glucose will be monitored with a YS1 continuous glucose monitor. The mechanism of insulin action on the CNS will be investigated in rats receiving stereotaxic injection of insulin with or without different concentrations of glucose, and different stereoisomers of glucose, as well as with non-metabolized glucose analogues. The long term effect of central hyperinsulinism will be studies in rats with stereotaxically placed permanent hypothalamic cannulae. Weight changes and feeding behavior will be studied after daily insulin or control saline injection into the cannulae.